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Rationale: Developmental vitamin D (DVD) deficiency is a candidate risk factor for developing schizophrenia in humans. In rodents DVD deficiency induces subtle changes in the way the brain develops. This early developmental insult leads to select behavioural changes in the adult, such as an enhanced response to amphetamine-induced locomotion in female DVD-deficient rats but not in male DVD-deficient rats and an enhanced locomotor response to the N-methyl- d-aspartate (NMDA) receptor antagonist, MK-801, in male DVD-deficient rats. However, the response to MK-801-induced locomotion in female DVD-deficient rats is unknown. Therefore, the aim of the current study was to further examine this behavioural finding in male and female rats and assess NMDA receptor density. Methods: DVD-deficient Sprague Dawley rats were assessed for locomotion, ataxia, acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR to multiple doses of MK-801. The NMDA receptor density in relevant brain regions was assessed in a drug-naive cohort. Results: DVD deficiency increased locomotion in response to MK-801 in both sexes. DVD-deficient rats also showed an enhanced ASR compared with control rats, but PPI was normal. Moreover, DVD deficiency decreased NMDA receptor density in the caudate putamen of both sexes. Conclusions: These results suggest that a transient prenatal vitamin D deficiency has a long-lasting effect on NMDA-mediated signalling in the rodent brain and may be a plausible candidate risk factor for schizophrenia and other neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. DVD deficiency in neonatal rats is associated with alterations in cellular development, dopamine metabolism, and brain morphology. DVD-deficient adult rats show novelty-induced hyperlocomotion and an enhanced locomotor response to MK-801, which can be ameliorated by pretreatment with the antipsychotic drug haloperidol. In this study, we examined locomotor responses of male and female juvenile and adult rats to a dose range of amphetamine. We also measured dopamine receptor and monoamine transporter densities in adult brain. Female DVD-deficient adult rats displayed an enhanced sensitivity to amphetamine-induced locomotion, an increased dopamine transporter density in the caudate–putamen and increased affinity in the nucleus accumbens compared with control females. By contrast, there were no differences between control and DVD-deficient male rats. Taken together, this suggests an alteration in the development of the dopamine system and on dopamine-mediated behaviors in female DVD-deficient rats, and this may be relevant to the underlying neurobiology of schizophrenia. [ABSTRACT FROM AUTHOR]